MX2008012575A - Non-homogenous dosage form coatings. - Google Patents

Abstract

The present invention is directed to liquid coating compositions and dosage forms having a continuous shell portion of a first composition and at least one discontinuous shell portion that is compositionally different located within the continuous shell portion. The present invention also provides a process for preparing a dosage form, which comprises coating a core with a continuous shell portion having a first composition and at least one discontinuous shell portion that is compositionally different located within the continuous portion, and then cooling the coated core. The coating compositions are particularly suited for forming shell coatings on solid pharmaceutical dosage forms.

Description

NON-HOMOGENEOUS COATINGS OF DOSAGE FORMS FIELD OF THE INVENTION The present invention relates to the coating of pharmaceutical dosage forms, wherein the coating forms at least one continuous cover portion having a first composition, and at least one portion of a discontinuous cover that is of different composition and is located within. of the continuous deck portion. The coatings are preferably produced in an injection molding system.

BACKGROUND OF THE INVENTION For several years oral dosage forms have been developed for pharmaceutical agents and dietary supplements. Among the most popular oral dosage forms are tablets, capsules and, more recently, gelcaps. Tablets are compressed or shaped dosage forms of any size or shape. Sometimes solid tablets of generally oblong shape can be referred to as caplets. Tablets are still popular with consumers; however, uncoated tablets have disadvantages such as medicinal taste, tendency to spray or laminate when packaged in jars (i.e., physical disintegration), or consumers' perception that they can not be easily swallowed. These limitations can be eliminated by coating the tablets with a polymeric coating. For most of the twentieth century, hard gelatine capsules were a popular dosage form for prescription and over-the-counter medications. The capsules are hard shell compartments made of two halves that include a body and a lid, wherein the lid overlaps partially and tightly with the body to enclose a dosif active ingredient cable. Very often the enclosed cable dosif ingredient is a powder, liquid, paste or similar non-solid form. Generally, empty gelatin hard capsules are produced by a conventional dip molding process, such as the one described on page 182 of "Pharmaceutical Dosage Forms and Drug Delivery Systems", 7th ed. (1999), by Howard C. Ansel, Loyd V. Alien Jr., and Nicholas G. Popovich, published by Lippincott Williams & Wilkins, Baltimore, Maryland. Consumers have found these capsules aesthetically pleasing, easy to swallow, and they mask the medicinal flavor of the contained drug. In addition, the bodies and caps of said capsules are often produced in different colors, resulting in a two-color capsule product having a better aesthetic appearance, as well as an improvement in the identification of the product and the recognition of the brand by the consumers. Many patients prefer capsules over coated or uncovered tablets, which has prompted pharmaceutical manufacturers to make some products in capsule form even when they are also available in tablet form. However, due to potential counterfeiting problems, capsules are no longer a preferred choice of supply for over-the-counter pharmaceutical agents. An alternative to capsule products are caplets, which are solid oblong tablets frequently coated with various polymers such as cellulose ethers, to improve their aesthetics, stability and ease of swallowing. Normally said polymers are applied to the tablets from a solution in organic solvents, or from an aqueous dispersion by means of aspersion. Other methods include coating tablets by sprinkling a gelatin coating solution; see, for example, U.S. Pat. UU Nos. 4,973,480 and 6,113,945. However, said spray-coated tablets lack the glossy surface and the elegance of the hard gelatin capsules. In addition, it is not commercially feasible to coat a tablet by spray with a different colored coating at each end. Another alternative of the capsule products are the "gelcaps", which are elegant dosage forms, preferred by the consumer, comprising solid tablets coated with a glossy gelatinous coating. Currently gelcaps are the most popular oral dosage forms. Several methods have been developed to produce gelcaps to provide counterfeit-proof capsule-type products. One category of such methods includes immersing the tablets, one half at a time, in gelatin coating solutions, which can be of two different colors; see, for example, US Pat. UU No. 4,820,524, or submerging half of the tablets of a first color in a gelatin coating solution of a second color; see, for example, US Pat. UU No. 6.1 13.945. Another category of such methods includes shrinking the capsule halves on a tablet form; see, for example, U.S. Pat. UU Nos. 5,415,868, 6,126,767, 5,464,631, 5,460,824, 5,317,849, 5,51 1, 361, 5,609,010, 5,795,588 and 6,080,426, and the publication of International Patent Application No. WO 97/37629. Another method includes sealing the body and cap of the capsule in the overlap joint between the two; see US Pat. UU No. 5,824,338. Another method of producing gelcaps is by means of a coating process wherein two separate films made of gelatinous material are applied on opposite sides of a tablet by means of a pair of rotating dies. A detailed description of this process is given for example in the US patents. UU Nos. 5,146,730 and 5,459,983, the total contents and descriptions of which are incorporated herein by reference.

BRIEF DESCRIPTION OF THE INVENTION The invention provides a dosage form having a coating, wherein the coating has at least one continuous covering portion having a first composition, and at least one discontinuous covering portion that is of different composition and is located within the covering portion continues. Preferably, the coating is produced in the dosage form using an injection molding system. The present invention also provides a method for preparing a dosage form, comprising coating a core with a continuous portion having a first composition, and at least one discontinuous portion that is of different composition and is located within the continuous portion, and then cooling the coated core.

DETAILED DESCRIPTION OF THE INVENTION As used herein, the term "dosage form" is applied to any solid object or semi-solid composition designed to contain a specific predetermined amount (dose) of a certain ingredient, for example an active ingredient as defined below. Suitable dosage forms may be drug delivery systems, including those for oral administration, oral administration, rectal administration, or compositions for delivering materials, vitamins and other nutraceutical agents, oral care agents, flavorings, and so on. Preferably, the dosage forms of the present invention are considered solid; however, they may contain liquid or semi-solid components. In a particularly preferred embodiment, the dosage form is an oral delivery system for delivering an active ingredient to the gastrointestinal tract of a human. The core can be any solid form. The core can be prepared by any suitable method including for example compression or molding. As used herein, "core" refers to a material that is wrapped or surrounded, at least partially, by another material on its outer surface region. Preferably, the core is a self-contained unit object, such as a tablet or capsule. Normally the core comprises a solid; for example, the core can be a compressed or molded tablet, hard or soft capsule, suppository, or a candied form such as a pill, nuégate, caramel, sugar paste or fat-based composition. In some embodiments, the core or a portion thereof may be in the form of a semi-solid or a liquid in the finished dosage form. For example, the core may comprise a capsule filled with liquid, or a semi-solid material of sugar paste. In embodiments in which the core comprises a fluid component, such as a plurality of granules or particles, or a liquid, preferably the core also comprises a shell component, such as a capsule shell, or a shell, to contain the shell. fluid material. In some particular embodiments in which the core comprises a wrapping component, the cover or cover portions of the present invention are in direct contact with the core wrapping component, which separates the shell of the fluid component from the core. The active ingredients suitable for use in this invention include for example pharmaceutical agents, minerals, vitamins and other nutraceutical agents, oral care agents, flavors, and mixtures thereof. Suitable pharmaceutical agents include analgesics, anti-inflammatory agents, antiarthritics, anesthetics, antihistamines, antitussives, antibiotics, anti-infective agents, antivirals, anticoagulants, antidepressants, antidiabetic agents, antiemetics, antiflatulents, antifungals, antispasmodics, appetite suppressants, bronchodilators, cardiovascular agents, agents for the central nervous system, central nervous system stimulants, decongestants, oral contraceptives, diuretics, expectorants, gastrointestinal agents, preparations against migraine, products for motion sickness, mucolytics, muscle relaxants, preparations for osteoporosis, polydimethylsiloxanes, respiratory agents, sleep aids, agents for the urinary tract, and mixtures thereof. In one embodiment, the active ingredient is selected from analgesics, anti-inflammatories and antipyretics, for example non-steroidal anti-inflammatory drugs (NSAIDs), which include propionic acid derivatives, for example ibuprofen, naproxen, ketoprofen, etc.; acetic acid derivatives, for example indomethacin, diclofenac, sulindac, tolmetin, etc.; phenamic acid derivatives, for example mefenamic acid, meclofenamic acid, flufenamic acid, etc.; biphenylcarbonyl acid derivatives, for example diflunisal, flufenisal, etc.; and oxicams, for example piroxicam, sudoxicam, isoxicam, meloxicam, and the like. In a particular embodiment, the active ingredient is selected from an NSAID derived from propionic acid, for example ibuprofen, naproxen, flurbiprofen, fenbufen, fenoprofen, indoprofen, ketoprofen, fluprofen, pirprofen, carprofen, oxaprozin, pranoprofen, suprofen, and pharmaceutically acceptable salts , derivatives, and combinations thereof. In another particular embodiment of the invention, the active ingredient can be selected from paracetamol, acetylsalicylic acid, ibuprofen, naproxen, ketoprofen, flubiprofen, diclofenac, cyclobenzaprine, meloxicam, roiecoxib, celecoxib, and pharmaceutically acceptable salts, esters, isomers, and mixtures of the same. In another embodiment of the invention, the active ingredient can be selected from phenylephrine, pseudoephedrine, phenylpropanolamine, chlorpheniramine, dextromethorphan, diphenhydramine, astemizole, terfenadine, fexofenadine, loratadine, desloratadine, guaifenesin, sidenefil, chlorphedianol, menthol, benzocaine, modafinil, cetirizine, mixtures thereof, and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof. The active ingredient or ingredients are present in the dosage form in a therapeutically effective amount, which is an amount that produces the desired therapeutic response after oral administration, and can be readily determined by the person skilled in the art. To determine such amounts, the particular active ingredient administered, the bioavailability characteristics of the active ingredient, the dosage regimen, the age and weight of the patient, and other factors known in the art should be considered. Typically, the dosage form comprises at least about 1% by weight, preferably the dosage form comprises at least about 5% by weight, for example at least about 25% by weight of a combination of one or more ingredients assets. In one embodiment, a core comprises a total of at least about 50% by weight, for example at least about 70% by weight, for example, at least about 80% by weight (based on core weight) of one or more active ingredients. The active ingredient or ingredients may be present in the dosage form in any form. For example, the active ingredient can be dispersed on the molecular scale, for example molten or dissolved, within the dosage form; or it may be in the form of particles which in turn may be coated or not. If the active ingredient is in the form of particles, the particles (whether coated or not) will normally have an average particle size of about 1-2000 microns. In one embodiment, such particles are crystals having an average particle size of about 1 -300 microns. In another embodiment, the particles are pellets or pellets having an average particle size of about 30-3000 microns, for example about 50-1000 microns, for example, about 100-800 microns.

In another embodiment, the active ingredient is coated in the form of particles for the purpose of masking the taste or modifying the release. The modified release includes prolonged, sustained, controlled and enteric release. If the active ingredient has a questionable taste and the dosage form is intended to be chewed or disintegrated in the mouth before being swallowed, the active ingredient may be coated with a taste masking coating, as is known in the art. Examples of suitable masking coatings are described, for example, in U.S. Pat. UU Nos. 4,851, 226; 5,075,114; and 5,489,436. Masked commercially available flavor active ingredients can also be used. For example, in the present invention paracetamol particles can be used which are encapsulated with ethylcellulose or other polymers by means of a coacervation process. Said encapsulated paracetamol by coacervation is commercially available from Eurand America, Inc. or Circa Inc. Additional suitable procedures for applying known taste masking coatings, include without limitation, fluid bed coating, coacervation, complex coacervation, spray drying and freezing. by sprinkling. The core may contain conventional ingredients such as fillers, which include water-soluble compressible carbohydrates such as sucrose, mannitol, sorbitol, maltitol, xylitol, erythritol, lactose, and mixtures thereof; conventional dry binders including cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, modified starch, and mixtures thereof, and in particular microcrystalline cellulose; sweeteners that include aspartame, acesulfame potassium, sucralose and saccharin; disintegrants such as microcrystalline cellulose, starch, sodium starch glycolate, entangled polyvinylpyrrolidone, crosslinked carboxymethyl cellulose; and lubricants such as magnesium stearate, stearic acid, talc and waxes. The tablet may also incorporate pharmaceutically acceptable adjuvants including, for example, preservatives, flavors, acidulants, antioxidants, glidants, surfactants and coloring agents. Normally the total amount of these other conventional ingredients will not exceed 25% of the weight of the tablet, approximately; that is, no more than about 20% of the weight of the tablet, or no more than about 15% of the weight of the tablet. The tablets of the present invention can be made by any known method. Conventional methods for tablet production include direct compression ("dry blending"), dry granulation followed by compression, and wet granulation followed by drying and compression. Other methods include the use of compression roller technology, such as a chilsonator apparatus or belt tensioning roller, or molding, casting or extrusion technology. All of these methods are known and described in detail, for example, in Lachman et al., "The Theory and Practice of Industrial Pharmacy", chapter 11 (3rd edition, 1986), which is incorporated herein by reference. In another embodiment, the core can be prepared by the compression methods and apparatuses described in the publication of the US patent application. UU No. 20040156902. Specifically, the core can be made using a rotary compression module comprising a filling zone, insertion zone, compression zone, ejection zone and purge zone, in a single apparatus having a double construction row of arrays, as shown in Figure 6 of the publication of the US patent application. UU No. 20040156902. The matrices of the compression module can then be filled with the help of vacuum, with filters located in or near each matrix. The purge zone of the compression module includes an optional dust recovery system to recover the excess dust from the filters and return the powder to the dies. In another modality, the core can be prepared by a wet granulation method, in which the active ingredient or ingredients, the appropriate excipients, and a solution or dispersion of a wet binder (e.g., an aqueous cooked starch paste, or polyvinylpyrrolidone solution) ), mix and granulate. Apparatus suitable for wet granulation include low shear mixers, eg planetary mixers; high shear mixers; and fluidized beds including rotating fluidized beds. The resulting granular material is dried and optionally dry blended with additional ingredients, for example adjuvants or excipients such as for example lubricants, colorants, etc. The final dry mixture is then suitable for compression by the methods described in the previous paragraph. The nucleus can be in a variety of different forms. For example, in one embodiment the core may be in the form of a truncated cone. In a modality it can be configured as a polyhedron, such as a cube, pyramid, prism or similar; or it may have the geometry of a spatial figure with some non-flat faces such as a cone, cylinder, sphere, bull, etc. Exemplary core shapes that may be used include the tablet shapes formed by the compression tool forms described by "The Elizabeth Companies Tablet Design Training Manual" (Elizabeth Carbide Die Co., Inc., p.7 (McKeesport, Pennsylvania) (incorporated herein by reference), as indicated below (the shape of the tablet corresponds inversely to the shape of the compression tool.) One or more outer coatings are applied on the core to form a shell. The coating differs from a layer of compressed powder normally depending on the degree of porosity, density and thickness.A compressed powder layer will generally have a higher degree of porosity and thickness, and a lower density.The present invention is a dosage form that has a coating provided on one or more cores from a mixture of materials, wherein a first component of the mixture flows in liquid form at temperatures equal to 37 ° C and greater, and a second component which is a solid particle capable of being suspended within the first component in liquid form. In one embodiment, the second component is solid at temperatures of at least 37 ° C. A liquid is a form of matter between a gas and a solid that has a defined volume but has no definite shape. For the purposes of this application, the individual particles are considered solid since each particle has a defined shape. In addition, a collection of such particles, although capable of flow, would not be considered a liquid due to the tendency of the particles to separate and the lack of homogeneous appearance under the normal flow conditions encountered in pharmaceutical coating operations. A mixture of immiscible liquids would still be considered "liquid" regardless of their ability to separate due to the fact that none of the individual components tends to separate or dissociate under normal flow conditions. After drying, the dosage form will have a coating characterized in that it is a substantially smooth continuous coating with particles dispersed therein. The particles may or may not be uniformly dispersed in the continuous coating. A continuous coating means that the coating forms regions of interconnection of a coating in which the particles are suspended. The continuous coating does not necessarily have to enclose the entire surface area of the underlying core. Openings or other designs may be provided in the continuous coating, in the known manner, which expose the otherwise underlying core surface. In some embodiments, the cover comprises a first cover portion and a second cover portion that are of different composition. In one embodiment, a first cover portion comprises the edible composition or matrix of the invention, and a second cover portion is of a composition different from the first cover portion. In such embodiments, the portions may contain different materials, such as for example polymers, active ingredients, sugars, sugar alcohols, plasticizers, surfactants, dyes, light diffraction flakes, and flavorings. As used herein, the term "of different composition" means that they have characteristics that are easily distinguishable by qualitative or quantitative chemical analysis, physical evidence or visual observation. For example, the first and second cover portions may contain different ingredients, or different concentrations of the same ingredients, or the first and second cover portions may have different physical or chemical properties, different functional properties, or be visually different. Examples of physical or chemical properties that may be different include hydrophilicity, hydrophobicity, hygroscopicity, elasticity, plasticity, tensile strength, crystallinity and density. Examples of functional properties that may be different include the rate or magnitude of dissolution of the material itself or of an active ingredient thereof, the rate of disintegration of the material, permeability to the active ingredients, permeability to water or aqueous medium, and the like. Examples of visual distinctions include size, shape, topography or other geometric features, color, hue, opacity and luster. Polymeric materials suitable for use in the formation of the discontinuous particle phase include any edible material that is solid at a temperature of at least about 37 ° C. Preferred polymers include water-soluble polymers such as polyalkylene glycols, including polyethylene glycol with a molecular weight scale of 3,350 to 20,000, polyethylene oxides and their derivatives, and sucrose esters; fats such as cocoa butter, hydrogenated vegetable oil such as palm oil, cottonseed oil, sunflower oil, and soybean oil; mono-, di- and triglycerides, phospholipids, linear hydrocarbons such as polyethylene wax, waxes such as carnauba wax, whale sperm, beeswax, candelilla wax, shellac wax, microcrystalline wax and paraffin wax; mixtures containing fat, such as chocolate; sugar in the form of an amorphous crystal like the one used to make solid caramel forms, sugar in a supersaturated solution like the one used to make sugar pastes; low moisture content polymer solutions, such as mixtures of gelatin and other hydrocolloids at water contents of up to about 30%, and those used to make "gummy" candied forms. In a particularly preferred embodiment, the particle-forming polymer is calcium alginate. Calcium ions induce entanglement reactions that promote the formation of particles. The particles preferably have a number average particle diameter of at least 10 microns, for example at least 30 microns, better at least 100 microns. On average, when the particles are measured using an electron microscope they have an average particle size smaller than about 3000 microns, less than about 1000 microns. The particles can be observed spherically and have a number average particle size between about 100 microns and about 3000 microns. In another embodiment, the particles may have a solids content of less than 100%, for example, 75%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 4%, 3%, 2% and 1%. Regardless of the presence of its liquid content, the polymer particles remain separated and dispersed within the film-forming polymer in its liquid form. The continuous film-forming polymer will also have a solids content. The solids content of the continuous film-forming polymer can be greater than 1%, 5%, 10%, 15%, 20%, 30% or 40%. In one embodiment, the polymer particles for the discontinuous phase have a solids content greater than the solids content of the continuous film forming polymer, which combine with each other to form a dispersion that can be used to provide a cover portion on a core that has high particle regions. The elevated regions are the result of a higher percentage of water that evaporates from the portion with a lower percentage of solids than the portion with a higher percentage of solids after drying. In another embodiment, the polymer particles for the discontinuous portion have a solids content lower than the solids content of the continuous film-forming polymer, which combine with each other to form a dispersion which can be used to provide a cover portion on a nucleus that has regions of depressed particles. Suitable materials for forming the liquid and finally continuous liquid phase of the dose form coating, or a portion thereof, include those comprising thermoplastic materials; film formers; thickeners such as gelling polymers or hydrocolloids; low melting point hydrophobic materials such as waxes and fats; non-crystallizable carbohydrates; etc. Suitable thermoplastic materials can be molded and shaped when they are hot and include both water soluble and insoluble polymers that are generally linear, non-interlaced, not tightly bonded with hydrogen bonding to adjacent polymer chains. Examples of suitable thermoplastic materials include: water-swellable thermoplastic cellulose derivatives, water-insoluble thermoplastic cellulose derivatives, thermoplastic vinyl polymers, thermoplastic starches, thermoplastic polyalkylene glycols, thermoplastic polyalkylene oxides, and amorphous glass sugar, et cetera, and derivatives, copolymers and combinations thereof. Examples of water-swellable thermoplastic cellulose derivatives that are suitable include hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), methylcellulose (MC). Examples of water insoluble thermoplastic cellulose derivatives that are suitable include cellulose acetate (CA), ethyl cellulose (EC), cellulose acetate butyrate (CAB), cellulose propionate. Examples of suitable thermoplastic vinyl polymers include polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Examples of suitable thermoplastic starches are described, for example, in U.S. Pat. UU No. 5,427,614. Examples of suitable thermoplastic polyalkylene glycols include polyethylene glycol. Examples of suitable thermoplastic polyalkylene oxides include polyethylene oxide having a molecular weight of from about 100,000 to about 900,000 Dalton. Other suitable thermoplastic materials include sugar in the form of an amorphous crystal such as that used to make solid caramel shapes. Substantially any known film former is suitable for use in the fluid material of the present invention. Examples of suitable film formers include, without limitation, water-soluble film-forming polymers, film-forming proteins, water-insoluble film-forming polymers, and pH-dependent film-forming polymers. In one embodiment, the film former for making the core or shell or portion thereof by molding, may be selected from cellulose acetate, type B ammonium methacrylate copolymer, shellac, hydroxypropylmethylcellulose, and polyethylene oxide, and combinations thereof. Water-soluble film-forming polymers that are suitable include water-soluble vinyl polymers such as polyvinyl alcohol (PVA); water soluble polycarbohydrates such as hydroxypropyl starch, hydroxyethyl starch, pululan, methylethyl starch, carboxymethyl starch, pregelatinized starches, and modified film-forming starches; water-swellable cellulose derivatives such as hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), hydroxyethylmethylcellulose (HEMC), hydroxybutylmethylcellulose (HBMC), hydroxyethylethylcellulose (HEEC), and hydroxyethylhydroxypropylmethylcellulose (HEMPMC); water-soluble copolymers such as copolymers of methacrylic acid and methacrylate ester, copolymers of polyvinyl alcohol and polyethylene glycol, copolymers of polyethylene oxide and polyvinylpyrrolidone; and derivatives and combinations thereof. Suitable film-forming proteins can be natural or chemically modified, and include gelatin, whey protein, myofibrillar proteins, coagulable proteins such as albumin, caffeine, caffeine isolates and caffeine isolates, soy protein and isolates of soy protein, zein; and polymers, derivatives, and mixtures thereof. Suitable water-insoluble film-forming polymers include, for example, ethylcellulose, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose acetate and its derivatives, acrylates, methacrylates, copolymers of acrylic acid, etc., and derivatives, copolymers, and combinations thereof. Suitable pH-dependent film-forming polymers include enteric cellulose derivatives, for example hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate; natural resins such as shellac and zein; enteric acetate derivatives such as for example polyvinyl acetate-phthalate, cellulose acetate phthalate, acetaldehyde dimethyl cellulose acetate; and enteric acrylate derivatives such as for example polymers based on polymethacrylate such as poly (methacrylic acid, methyl methacrylate): 2, which is commercially available from Rohm Pharma GmbH under the trademark EUDRAGIT S, and poly (methacrylic acid, methyl methacrylate) 1: 1, which is commercially available from Rohm Pharma GmbH under the trademark EUDRAGIT L, and the like, and derivatives, salts, copolymers, and combinations thereof. A hydroxypropylmethylcellulose compound suitable for use as a water soluble film-forming thermoplastic polymer is "HPMC 2910", which is a cellulose ether having a degree of substitution of about 1.9 and a molar hydroxypropyl substitution of 0.23, and containing , based on the total weight of the compound, from about 29% to about 30% methoxyl groups, and from about 7% to about 12% hydroxypropyl groups. HPMC 2910 is commercially available from Dow Chemical Company under the trademark METHOCEL E. METHOCEL E5, which is a grade of HPMC-2910 suitable for use in the present invention, has a viscosity of about 4 to 6 cps (4 to 6 millipascales -second) at 20 ° C in a 2% aqueous solution, determined by an Ubbelohde viscometer. Similarly, METHOCEL E6, which is another grade of HPMC-2910 suitable for use in the present invention, has a viscosity of about 5 to 7 cps (5 to 7 millipascales-seconds) at 20 ° C in an aqueous solution at 2 ° C. %, determined by an Ubbelohde viscometer. METHOCEL E15, which is another grade of HPMC-2910 suitable for use in the present invention, has a viscosity of about 15,000 cps (15 millipascales-seconds) at 20 ° C in a 2% aqueous solution, determined by an Ubbelohde viscometer . As used herein, "degree of substitution" will mean the average number of substituent groups attached to an anhydroglucose ring, and "molar substitution of hydroxypropyl" will mean the number of moles of hydroxypropyl per mole of anhydroglucose. A suitable copolymer of polyethylene glycol and polyvinyl alcohol is commercially available from BASF Corporation under the trademark KOLLICOAT IR. As used in this, "modified starches" includes starches that have been modified by interlacing, chemically modified to improve stability or optimize yield, or physically modified to improve solubility properties or optimize yield. Examples of chemically modified starches are well known and typically include starches that have been chemically treated to replace some of their hydroxyl groups with ester or ether groups. Entanglement, as used herein, can occur in modified starches when two hydroxyl groups are chemically linked to neighboring starch molecules. As used herein, "pregelatinized starches" or "instant starches" refers to modified starches that have been pre-mopped and then dried to improve their solubility in cold water. Suitable modified starches are commercially available from various suppliers, such as for example A. E. Staley Manufacturing Company, and National Starch &; Chemical Company. A suitable modified film-forming starch includes the pregelatinized waxy corn-derived starches, which are commercially available from National Starch & Chemical Company under the PURITY GUM and FILMSET brands, and derivatives, copolymers, and mixtures thereof. Said waxy corn starches typically contain, based on the total weight of the starch, from about 0% to about 18% amylose, and from about 100% to about 88% amylopectin. Another suitable modified film-forming starch includes the hydroxypropylated starches, in which some of the hydroxyl groups of the starch have been etherified with hydroxypropyl groups, usually by treatment with propylene oxide. An example of a suitable hydroxypropyl starch having film-forming properties is available from Grain Processing Company under the trademark PURE-COTE B790.

Tapioca dextrins suitable for use as film formers include those available from National Starch & Chemical Company under the trademarks CRYSTAL GUM or K-4484, and derivatives thereof, such as tapioca-derived modified food starch, which is available from National Starch and Chemical under the trademark PURITY GUM 40, and copolymers and mixtures thereof. Any thickener known in the art is suitable for use in the fluid material of the continuous phase or solids of the discontinuous phase of the present invention. Examples of such thickeners include, without limitation, hydrocolloids (also referred to herein as "gelling polymers"), clays, gelling starches and crystallizable carbohydrates, and derivatives, copolymers and mixtures thereof. Examples of suitable hydrocolloids are alginates, agar, guar gum, locust bean gum, carrageenan, tara, gum arabic, tragacanth, pectin, xanthan, gelan, maltodextrin, galactomannan, pustulan, laminarin, scleroglucan, gum arabic, inulin, pectin, whelan, rhamsan, zooglan, methylan, chitin, cyclodextrin and chitosan. Examples of suitable clays include smectites such as bentonite, kaolin and laponite; magnesium trisilicate, aluminum magnesium silicate, etc., and derivatives and mixtures thereof. Examples of suitable gelling starches include starches hydrolyzed with acid, and derivatives and mixtures thereof. Other suitable thickening hydrocolloids include low moisture content polymer solutions, such as mixtures of gelatin and other hydrocolloids, at water contents of up to about 30%, such as, for example, those used to make "gummy" jams. Other suitable thickeners include crystallizable carbohydrates and the like, and derivatives and combinations thereof. Suitable crystallizable carbohydrates include monosaccharides and oligosaccharides. Of the monosaccharides, the aldohexoses are preferred, for example, the D and L isomers of alose, altrose, glucose, mannose, gulose, iodine, galactose, talose, and the ketohexes, for example, the D and L isomers of fructose and sorbose. , together with its hydrogenated analogs: for example, glucitol (sorbitol) and mannitol. Of the oligosaccharides, the 1,2-disaccharides sucrose and trehalose, the 1,4-disaccharides maltose, lactose and cellobiose, and the 1,6-disaccharides gentiobiose and melibiose, as well as the trisaccharide raffinose, together with the isomerized form are preferred. of sucrose known as isomaltulose and its hydrogenated analog isomalt. Other hydrogenated forms of reducing disaccharides (such as maltose and lactose) are also preferred, for example, maltitol and lactitol. In addition, the hydrogenated forms of the aldopentoses are preferred: for example, D- and L-ribose, arabinose, xylose and lyxose, and the hydrogenated forms of the aldotetroses: for example, D- and L-erythrose and threose, and are exemplified by xylitol and erythritol, respectively. Any plasticizer known in the pharmaceutical field is suitable for use in the composition of the continuous phase or in the solid particles of the discontinuous phase, and may include, without limitation, polyethylene glycol; glycerin; sorbitol; triethyl citrate; tributyl citrate; dibutyl sebacate; vegetable oils such as castor oil; surfactants such as polysorbates, sodium lauryl sulfate and sodium dioctyl sulfosuccinate; propylene glycol; glycerol monoacetate; glycerol diacetate; glycerol triacetate; natural gums; and mixtures thereof. In solutions containing a cellulose ether film former, an optional plasticizer may be present in an amount, based on the total weight of the solution, of from about 0% to about 40%. In one embodiment of the invention, the liquid fluid material to form the continuous phase of the coating comprises gelatin as the gelling polymer. Gelatin is a natural thermogelling polymer. It is an insipid and colorless mixture of proteins derived from the albuminous class that is regularly soluble in hot water. Two types of gelatin are commonly used - type A and type B. Gelatin type A is a derivative of raw materials treated with acid. Type B gelatin is a derivative of alkali-treated raw materials. The moisture content of gelatin, as well as its gel strength (Bloom), composition and original processing conditions of gelatin, determine its transition temperature between liquid and solid. Bloom is a standard measure of the strength of a gelatin gel, and correlates roughly with molecular weight. The Bloom is defined as the weight in grams that is required to move 4 mm plastic plunger of 1.27 cm in diameter in a 6.67% gelatin gel, which has been maintained at 10 ° C for 17 hours. In a preferred embodiment, the fluid material is an aqueous solution comprising pig skin gelatin at 20% Bloom 275, 20% Bloom 250 gelatin, and about 60% water. Suitable xanthan gums include those available from C. P. Kelco Company, under the trademarks KELTROL 1000, XANTROL 180 or K9B310. Suitable clays include smectites such as bentonite, kaolin and laponite, magnesium trisilicate, aluminum magnesium silicate, etc., and derivatives and mixtures thereof. "Acid hydrolyzed starch", as used herein, is a type of modified starch that results from treating a suspension of starch with dilute acid at a temperature below the starch gelatinization point. During acid hydrolysis, the granular form of the starch is maintained in the starch suspension, and the hydrolysis reaction is terminated by neutralization, filtration and drying, once the desired degree of hydrolysis has been achieved. As a result, the average molecular size of the starch polymers is reduced. Acid-hydrolyzed starches (also known as "low-boiling starches") tend to have a much lower hot viscosity than the native starch itself, as well as a strong tendency to gel when cooled. The term "gelling starches", as used herein, includes starches which, when combined with water and heated to a temperature sufficient to form a solution, then form a gel upon cooling to a temperature below the point of gelation. of starch.

Examples of gelling starches include, without limitation, acid hydrolyzed starches such as those available from Grain Processing Corporation under the tradename PURE-SET B950; hydroxypropyl starch diphosphate, such as that available from Grain Processing Corporation under the trademark PURE-GEL B990, and mixtures thereof. Suitable low melting point hydrophobic materials include fats, fatty acid esters, phospholipids and waxes. Examples of suitable fats include hydrogenated vegetable oils, such as, for example, cocoa butter, hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenated sunflower oil and hydrogenated soybean oil; and free fatty acids and their salts. Examples of suitable fatty acid esters include fatty acid esters of sucrose, monoglycerides, diglycerides and triglycerides, glyceryl behenate, glyceryl palmito stearate, glyceryl monostearate, glyceryl tristearate, glyceryl trilaurilate, glyceryl myristate, Glyco Wax-932 , lauroyl macrogol-32 glycerides and stearoyl macrogol-32 glycerides. Examples of suitable phospholipids include phosphatidylcholine, phosphatidylserine, phosphatidylinositol and phosphatidic acid. Examples of suitable waxes include carnauba wax, whale sperm wax, beeswax, candelilla wax, shellac wax, microcrystalline wax and paraffin wax; mixtures containing fat such as chocolate; etc. Suitable non-crystallizable carbohydrates include non-crystallizable sugars such as polydextrose, and starch hydrolysates, for example, glucose syrup, corn syrup and high fructose corn syrup; and non-crystallizable sugar alcohols such as maltitol syrup. In some embodiments, at least one covering of the cover or the cover portions is in direct contact with the core. In some other embodiments, the inner covering of the cover or the cover portions is in direct contact with a sub-coating substantially surrounding the core. In some embodiments, the cover or a cover portion may comprise one or more openings. In embodiments where one or more coverings are applied to the core by the cover or molding portion, at least a portion of the cover surrounds the core such that the inner surface of the cover receives substantially adjusted on the outer surface of the core. As used herein, the term "substantially adjusted" means that the inner surface of the cover has peaks and valleys or depressions and projections that correspond substantially inverse to the peaks and valleys of the outer surface of the core. In one embodiment, the dosage form of the invention comprises: a) a core containing an active ingredient; b) an optional subrecovering that substantially covers the core; and c) a coating comprising at least a first and a second covering portion residing on the surface of the sub-coating. The term "cover portion" should not be considered as requiring a physical difference or composition in matter. Rather, a cover portion could be part of one and the same continuous cover section, but it is distinguished from another portion with respect to the core region in contact with some other similar distinguishable feature. As used herein, "substantially covering" means that at least about 95% of the surface area of the core is covered by the sub-coating. The use of the subcoat is well known and is described, for example, in US Pat. UU Nos. 3,185,626, which is incorporated herein by reference. In a preferred embodiment, the discontinuous portion of the cover facilitates a more rapid disintegration of the dosage form. The integrity of the cover depends on the uniformity of the film on the cover. The discontinuous portion creates spaces in the film that interrupt this uniformity. When the coated dose form is placed in a liquid medium, the continuous portions of the cover will disintegrate more quickly since the film is not uniform and breaks more easily. In one embodiment, the dosage form may contain, based on the total dry weight of the dosage form, from about 1% to about 99%, for example from about 1% to about 50% of the shell comprising the continuous portion , and from about 0.1% to about 75%, for example from about 0.1% to about 40%, of the discontinuous portion. The cover may contain, based on the total weight of the cover, from about 40% to about 99%, for example from about 40% to about 80% of the continuous portion, and from about 1% to about 50%, for example from about 1% to about 40% of the discontinuous portion. In one embodiment, the discontinuous phase is present in the non-crystalline or amorphous phase, both in the liquid coating composition and in the solid dry dose form. In this embodiment, the discontinuous phase is substantially free of crystalline materials. In one embodiment, a dispersion of the composition comprising the continuous film-forming polymer and a polymeric particle for the discontinuous phase is used to prepare the shell. In particular, the polymer particles and the liquid gelling polymer are dispersed in an aqueous solution. The dispersion is applied to a core, for example by molding, dipping, coating or other means. Preferably, the dispersion is applied to the core by molding. After applying the dispersion to the core, it is cooled, preferably at a relatively high temperature. Injection molding is performed by injecting the dispersion into a hot molding chamber, such as for example that described in US Pat. UU No. 6,326,026. In this embodiment, the dispersion comprises the polymer particle dispersed in a liquid carrier comprising the gelling polymer. The dispersion cools and solidifies in the mold chamber in the pre-established shape (ie, having the shape of the mold). In addition, the internal surface of the mold defining the cavity can be provided with channels that guide the particles of the dispersion and cause them to be placed in predetermined patterns on the surface of the core. In alternative embodiments, the cover is applied by known methods, such as immersion, which is described, for example, in US Pat. UU No. 4,820,524; or the coating that is described, for example, in U.S. Pat. UU Nos. 6,482,516 and 5,146,730, using a previously prepared film. The dispersion for making the cover by injection molding may optionally comprise adjuvants or excipients which may comprise up to 30% by weight of the dispersion. Examples of suitable adjuvants or excipients include anti-adherents, humectants, surfactants, defoamers, colorants, flavors, sweeteners, opacifiers, and the like. In one embodiment, before injection molding on a core, the material of the discontinuous phase is maintained in a tank and the material of the continuous phase is maintained in a separate tank. The materials are mixed online during the injection process using a static in-line mixer. The degree of mixing is controlled by the speed of the static mixer, which depends on the flow velocity of the two materials in the mixer. The speed at which the materials are injected depends on the degree of positive air pressure that is connected to each tank. The degree of air pressure can vary from about 0.7 kg / cm2 to about 7 kg / cm2. In another embodiment, the two materials are mixed in a common solution and kept in a single tank before application to the core. In embodiments where the coatings are prepared by molding, the continuous regions of the coatings are generally substantially free of pores in the diameter range of 0.5 to 5.0 microns, that is, they have a pore volume in the diameter scale of pore 0.5 to 5.0 microns, less than about 0.01 cc / g, preferably less than about 0.005 cc / g. Typical compressed materials have pore volumes, in this diameter scale, greater than about 0.02 cc / g. Pore volume, pore diameter and density can be determined using a PoreMaster 60 mercury intrusion porosimeter from Quantachrome Instruments and the associated computer software program, known as "Porowin". The procedure is documented in the PoanMaster operation manual of Quantachrome Instruments. The PoreMaster determines both the pore volume and the pore diameter of a solid or powder, by means of the forced intrusion of a non-wetting liquid (mercury), which includes evacuating the sample in a sample cell (penetrometer), filling the mercury cell to surround the sample with mercury, apply pressure to the sample cell: (i) by means of compressed air (maximum up to 3.5 kg / cm2); and (ii) by means of a hydraulic pressure generator (oil) (maximum up to 4,200 kg / cm2). The volume entered is measured by a change in capacitance as the mercury moves from outside the sample to its pores under the applied pressure. The diameter of the corresponding pore size (d) at which the intrusion takes place, is calculated directly from the so-called "Washburn" equation: ú = - (4y (eos T) /?), Where? is the surface tension of the liquid mercury, T is the contact angle between the mercury and the surface of the sample, and P is the applied pressure. Suitable solvents for optional use as components of the fluid material for molding the cover, or a portion thereof, include water; polar organic solvents such as methanol, ethanol, isopropanol, acetone, et cetera; and non-polar organic solvents such as methylene chloride, etc.; and mixtures thereof. The cover portions of the present invention can be prepared by molding, using a solvent-free process, or a solvent-based process, and depending on the method used, usually comprises a variety of excipients that are useful for imparting the desired properties to the portions covering. The cover portions may optionally comprise one or more additional active ingredients. In one embodiment, the continuous portion or the discontinuous portion may optionally comprise a flavoring or sensing agent. How it is used here, a "sensitive agent" is a chemical agent that causes a sensory effect in the mouth, nose or throat, different from an aroma or flavor. Examples of such sensory effects include, without limitation, cold, heat, tingling, mouth-watering sensation (succulent sensation), astrigence, et cetera. Sensory agents suitable for use in the present invention are commercially available and can be purchased for example from International Flavor &; Fragrances. Each coating in the cover layer may have individual thicknesses in the range of about 50 microns to about 4000 microns. In some preferred embodiments, at least one coating in the cover layer has a thickness of less than 800 microns. In embodiments wherein at least one coating of the cover layer (or part thereof) is prepared in a solventless molding process, said cover layer (or part thereof) typically has a thickness of approximately 500 microns. at about 4000 microns, for example from about 500 microns to about 2000 microns, say from about 500 microns to about 800 microns, or from about 800 microns to about 1, 200 microns. In embodiments where the cover layer (or part thereof) is prepared by a solvent-based molding process, the cover layer typically has a thickness of less than about 800 microns, for example from about 100 microns to about 600 microns. microns, say from about 150 microns to about 400 microns.

In other particular embodiments, the thickness will vary between the continuous and discontinuous regions of the cover, and the average thickness of a region is at least 10% greater than the smallest or largest thickness of the other region. In other words, in a mode where the incorporation of a discontinuous phase produces a coating that has a concave dimple appearance, the average thickness of the continuous phase will be at least 10% greater than the average smallest thickness measured from the base of each concave dimple. In a modality wherein the incorporation of a discontinuous phase produces a coating that has a high dimpled appearance, the average thickness of the continuous phase will be at least 10% less than the largest average thickness measured from the top of each dimple high. In one embodiment, the dimple portions of the film in the concave dimple appearance mode have a diameter of between about 30 microns and 3000 microns, or from about 100 microns to 1000 microns, or from about 300 microns to about 1000 microns. mieras In another embodiment, the dimple portions of the film in the high dimple appearance mode have a diameter of between about 30 microns and 3000 microns, or from about 100 microns to 1000 microns, or from about 300 microns to about 1000 microns . In another embodiment, the continuous phase and the discontinuous phase contain the same amount of dissolved solids in the liquid dispersion phase before their application as a cover on a dosage form. In this embodiment, the resulting film will be substantially smooth after drying, with no raised or dimpled portions. The continuous phase and the discontinuous phase will nevertheless be of different composition. The following non-limiting examples are provided to further illustrate the disclosed invention.

Part A: Preparation of a gelatin-based coating solution containing alginate microbeads Preparation of alginate-based microbeads Microbeads are prepared by gradually dripping 20 ml of the alginate solution (1.5%, Kelton HV from CP Kelco) in 300 ml. of a calcium chloride solution (0.5%), with stirring and mixing with a magnetic stir bar, using a dropper, and a Novamatrix® electrostatic globule generator. The resulting spherical gel globules are then filtered through a 100 mesh screen and washed with pure water. Preparation of the gelatin-based coating solution containing alginate globules. The gelatine solution is prepared by adding 70 g of pig skin gelatin 275 Bloom in 130 g of pure water preheated to 55 ° C, with stirring at 100 rpm. All the alginate globules made in the first step are then added to the gelatin solution, mixing at the same time at 100 rpm.

Part B: Preparation of the gelatin-based coating solution containing wax-based micro-lobes. Preparation of wax based globules. The microbeads are prepared by emptying a wax composition consisting of: 16.25 g of Castrowax MP 80 (the supplier is Caschem) and 0.029 g of yellow dye # 11 D &C (the supplier is Sensient, Inc.), previously melted at 90 ° C, to a container containing 210 g of pure water with Gelucire 50/13 as a dispersant, previously heated to 85 ° C. Then, the mixture is stirred vigorously at 800 rpm for 2 minutes before cooling. During the cooling process the dispersed oily drops solidify. The waxy globules are collected by filtration and washed with cold pure water. Preparation of the gelatin-based coating solution containing wax globules: The gelatin solution is prepared by adding 105 g of 250 Bloom bone gelatine to 195 g of pure water previously heated to 55 ° C, with stirring at 100 rpm. All the wax globules made in the first step are then mixed with the gelatin solution.

Part C: Compressed tablets The following ingredients are thoroughly mixed in a plastic bag, from one end to the other, for approximately 3 minutes: 89.4 parts of USP paracetamol (590 mg / tablet) and 8.0 parts of synthetic wax X-2068 T20 (53 mg / tablet). Then 2.1 parts of sodium starch glycolate (EXPLO ) (13.9 mg / tablet) and 0.09 parts of silicon dioxide (0.6 mg / tablet) are added to the bag and mixed well from one end to the other for approximately 3 minutes. Then 0.36 parts magnesium stearate NF (2.4 mg / tablet) is added to the bag, and the ingredients are again mixed from one end to the other for about 1 minute. The resulting dry mixture is compressed into tablets in a rotary tablet compression module using extra-deep 1.1 cm concave tablet tools. The compression module is a double row rotating apparatus comprising a filling zone, insertion zone, compression zone, ejection zone and purge zone. The matrices of the compression module are filled with the help of vacuum, with mesh sieve filters located in matrix wall holes of each matrix. The resulting tablets (cores) have an average weight of 660 mg, thickness of 7.77 mm, and hardness of 3.2 kp.

Part D: Coating of tablets The tablets of part B are taken to a molding module by means of a transfer device. A part of the tablets is coated with gelatin-based solutions containing the alginate globules of part E, and a portion of the tablets are coated with the gelatin-based solutions containing the wax-based globules of part B, form a cover. A molding module applies the cover to the tablets. The tablets are transferred to the mold assemblies, which are then closed over the tablets. The fluid material, which is heated to a fluid state in a tank, is injected into the mold cavities created by the closed mold assemblies. The temperature of the cover fluid material is then reduced by hardening it. The mold assemblies are opened and the coated cores are ejected. The coating is done in two steps, each tablet half being coated separately.

Claims (26)

NOVELTY OF THE INVENTION CLAIMS

1. A liquid pharmaceutical dosage coating composition comprising: (a) a shell-forming component comprising a dispersion of: (i) at least one film-forming polymer in liquid form, which is liquid at temperatures of 37 ° C or greater, and (ii) at least one particle-forming polymer in the form of a solid particle, for a discontinuous phase which is dispersed in said polymer in liquid form of (i); wherein the solid particles have an average particle size in number of at least 30 microns.

2. - The liquid pharmaceutical dosage coating composition according to claim 1, further characterized in that the film-forming polymer (at least one) is insoluble in water.

3. - The liquid pharmaceutical dosage coating composition according to claim 1, further characterized in that the film-forming polymer (at least one) is a gelling polymer soluble in water or swellable in water.

4. - The liquid pharmaceutical dosage coating composition according to claim 3, further characterized in that the gelling polymer consists essentially of at least one gelatin.

5. The liquid pharmaceutical dosage coating composition according to claim 2, further characterized in that the water-insoluble film-forming polymer is entangled.

6. The liquid pharmaceutical dosage coating composition according to claim 1, further characterized in that the particle-forming polymer (at least one) is insoluble in water.

7. - The liquid pharmaceutical dosage coating composition according to claim 6, further characterized in that the water-insoluble particle that forms the particle is entangled.

8. - The liquid pharmaceutical dosage coating composition according to claim 1, further characterized in that the particles have a number average particle size of less than about 3000 microns.

9. - The liquid pharmaceutical dosage coating composition according to claim 8, further characterized in that the particles have an average particle size smaller than about 1000 microns.

10. The liquid pharmaceutical dosage coating composition according to claim 8, further characterized in that the particles are spherically shaped and have a number average particle size of between about 30 microns and about 3000 microns.

11. The liquid pharmaceutical dosage coating composition according to claim 1, further characterized in that the solid particles are amorphous.

12. The liquid pharmaceutical dosage coating composition according to claim 1, further characterized in that the solid particles are soluble in water.

13. - A solid pharmaceutical dosage form comprising a core and at least one coating layer comprising a solid continuous film having differentiated regions of different composition dispersed therein.

14. - The solid pharmaceutical dosage form according to claim 13, further characterized in that the core comprises a tablet of compressed powder.

15. The solid pharmaceutical dosage form according to claim 13, further characterized in that at least one coating layer has a dimpled concave surface area comprising portions with dimples.

16. - The solid pharmaceutical dosage form according to claim 13, further characterized in that the diameter of the dimpled portions in said dimpled surface area is between about 30 microns and about 3000 microns.

17. - The solid pharmaceutical dosage form according to claim 15, further characterized in that the diameter of the dimple portions in said concave dimple surface area is between about 30 microns and about 3000 microns.

18. The solid pharmaceutical dosage form according to claim 15, further characterized in that the thickness of the solid continuous film is, on average, at least 10% greater than the smallest thickness of the solid continuous film and the regions differentiated overlays of different composition in said regions having a concave surface area.

19. The solid pharmaceutical dosage form according to claim 13, further characterized in that at least one coating layer has a high dimple surface area comprising portions of dimples.

20. The solid pharmaceutical dosage form according to claim 19, further characterized in that the thickness of the solid continuous film is, on average, at least 10% less than the largest thickness of the solid continuous film and the region differentiated overlay of different composition in said regions having a high dimple surface area.

21. The solid pharmaceutical dosage form according to claim 13, further characterized in that the differentiated regions of different composition have a greater water solubility than the solid continuous film.

22. - A method for preparing a solid dose form, comprising coating a core containing a pharmaceutical active ingredient with the composition claimed in claim 1.

23. - The method according to claim 22, further characterized in that the solid particles are sufficiently hydrated to deform in an injection molding system.

24. - A method for preparing a dosage form of core and shell, comprising: (a) forming a compressed core containing at least one active pharmaceutical ingredient in a tablet compression machine; and (b) coating the compressed core with the composition claimed in claim 1.

25. - A method for preparing a dosage form of core and shell, comprising: (a) forming a compressed solid core containing at least one active pharmaceutical ingredient in a tablet machine; (b) introducing the compressed core into a mold cavity; and (c) injecting the composition claimed in claim 1 into the mold cavity to coat at least a portion of the compressed core.

26. - A method for preparing a dosage form of core and shell, comprising: (a) forming a compressed solid core containing at least one active pharmaceutical ingredient in a tablet machine; (b) introducing the compressed core into a mold cavity; (c) injecting the composition claimed in claim 1 into the mold cavity to coat at least a portion of the compressed core; (d) rotating the mold cavity; and (e) injecting a curable liquid composition into said mold for coating at least a second portion of the compressed core.